SH3 domains: modules of protein–protein interactions

Abstract

Src homology 3 (SH3) domains are involved in the regulation of important cellular pathways, such as cell proliferation, migration and cytoskeletal modifications. Recognition of polyproline and a number of noncanonical sequences by SH3 domains has been extensively studied by crystallography, nuclear magnetic resonance and other methods. High-affinity peptides that bind SH3 domains are used in drug development as candidates for anticancer treatment. This review summarizes the latest achievements in deciphering structural determinants of SH3 function.

Solution structures of the SH3 domains from Shank scaffold proteins and their interactions with Cav1.3 calcium channels

“…), all three structures are almost identical to one another. All structures have a typical SH3 fold, which contains a small β‐barrel consisting of five antiparallel β‐strands connected by three loops (RT loop, n‐Src‐loop and distal‐loop from the N‐terminus) and a small 3 10 helix . The backbone rmsd is 0.53 Å when they are overlaid using the backbone heavy atoms in folded regions (residues 559–609 of SNK1‐SH3, residues 530–582 of SNK2‐SH3, and residues 476–527 of SNK3‐SH3) (Fig.…”

Autosomal dominant progressive hyperpigmentation and lentigines in a Japanese pedigree due to a missense mutation near the C-terminus ofKIT

“…4 SH3 domains bind proline-rich sequences, particularly those carrying the PxxP motif. 4 We speculate that an adaptor protein having an SH3 domain may bind to the mutated KIT via this newly generated SH3 domain-binding motif and may cause abnormal KITLG/KIT signalling.…”

“…As one of six Src‐family protein tyrosine kinase domains, the SH3 domain plays significant roles in substrate recognition, membrane localization and regulation of tyrosine kinase activity . SH3 domains bind proline‐rich sequences, particularly those carrying the PxxP motif . We speculate that an adaptor protein having an SH3 domain may bind to the mutated KIT via this newly generated SH3 domain‐binding motif and may cause abnormal KITLG/KIT signalling.…”

“…g,h). As one of six Src‐family protein tyrosine kinase domains, the SH3 domain plays significant roles in substrate recognition, membrane localization and regulation of tyrosine kinase activity . SH3 domains bind proline‐rich sequences, particularly those carrying the PxxP motif .…”

Novel genetic variants associated with mRNA expression of signal transducer and activator of transcription 3(STAT3) gene significantly affected goat growth traits

“…The family of STATs comprises seven structurally and functionally related members: STAT1, STAT2, STAT3, STAT4, STAT5a, STAT5b, and STAT6, which all contain the Src homology domain 2 (SH2) domain, the Src homology domain 3 (SH3) domain, and a tyrosine phosphorylation site at their carboxyl-terminal region (Alvarado et al, 2010;Kurochkina and Guha, 2013). While most STAT proteins have been studied extensively, STAT3 remains to be fully characterized (Stark and Darnell, 2012).…”